Stereospecifïc total synthesis of (±)-cassipurine, an alkaloid from rhizophoraceae

Abstract

Two isomeric 1α,2α-epoxy- and 1β,2β-epoxypyrrolizidines have been obtained from 1,2-dehydropyrrolizidine. The structure of both isomers has been determined enabling a study of the stereochemistry of their reactions with a number of sulfur-containing nucleophilic reagents. The BzS− anion has been shown to stereospecifically attack the C2 carbon atom of both compounds. In the three-stage process 1β,2β-epoxypyrrolizidine was transformed into 1α,2α-epithiopyrrolizidine, which reacts stereospecifically with benzylthiol to yield 1α-(2β-thiobenzylpyrrolizidine)-thiol. This, in turn, oxidizes in air to give a mixture of three diastereomeric 1α,1′α-dithio-2β,2′β-dithiobenzyldipyrrolizidines. These diastereomers were chromatographically separated into the racemic mixture and the meso diastereomer. Treatment of the racemic mixture with Na/liquid NH3 induced debenzylation without cleavage of the disulfide bond. The resulting enantiomeric α,1′α-dithio-2β,2′β-dimercaptodipyrrolizidines were oxidized in air to give racemic cassipurine.